CN117000304A - Application of cyclic quaternary ammonium base in preparation of racemic nicotine - Google Patents

Application of cyclic quaternary ammonium base in preparation of racemic nicotine Download PDF

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CN117000304A
CN117000304A CN202310977525.XA CN202310977525A CN117000304A CN 117000304 A CN117000304 A CN 117000304A CN 202310977525 A CN202310977525 A CN 202310977525A CN 117000304 A CN117000304 A CN 117000304A
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quaternary ammonium
ammonium base
nicotine
cyclic
reaction
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陈欢
韩书磊
付亚宁
王红娟
田雨闪
侯宏卫
胡清源
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National Tobacco Quality Supervision and Inspection Center
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0239—Quaternary ammonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B55/00—Racemisation; Complete or partial inversion
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The application relates to application of cyclic structure quaternary ammonium base in preparation of racemic nicotine, wherein the cyclic structure quaternary ammonium base is shown as a formula I or a formula II:

Description

Application of cyclic quaternary ammonium base in preparation of racemic nicotine
Technical Field
The application belongs to the technical field of preparation of racemic nicotine, and particularly relates to application of quaternary ammonium base with a cyclic structure in preparation of racemic nicotine.
Background
Nicotine is an important quality element in tobacco products and is the most important alkaloid in tobacco. Related researches show that the composition has strong physiological activity and has regulating effect on the central nervous system, the peripheral nervous system and the auxiliary kidney medulla. In addition, nicotine has a wide range of applications in the fields of medicine, agricultural chemicals, and the like. The isoniazid, nicotinamide, nicotinic acid and the like are synthesized from nicotine serving as raw materials in medicine, and have good curative effects on tuberculosis resistance, depression resistance, bacteria resistance, parkinsonism treatment, oxidation resistance, memory, learning disorder and the like. In the aspect of pesticides, the nicotine can be used for disinfection of poultry living environment, and also used as plant growth regulator, pesticide and the like.
There is one chiral center in the nicotine molecule, so there will be two enantiomers, namely (R) - (+) -nicotine (R-nicotine) and (S) - (-) -nicotine (S-nicotine), as shown below. In nature, tobacco and tobacco products contain mainly S-nicotine.
Chiral has a general and important nature. A pair of enantiomers has many of the same physicochemical properties in an achiral environment, e.g. the same melting point, the same solubility, etc. In chiral environments, however, the properties of a pair of enantiomers tend to differ or even be opposite, as the pair of enantiomers differ in their effect. For example, L-Dopa (L-Dopa) for the treatment of Parkinson's disease can be successfully enzymatically decarboxylated in humans to form pharmacologically active species, whereas if D-Dopa is administered, it cannot be catalytically decarboxylated to affect the health. Ibuprofen (Ibuprofen) in the S-configuration is a non-steroidal high-efficiency antipyretic analgesic, whereas Ibuprofen in the R-configuration is totally inactive and only increases the metabolic burden in the body.
Racemic nicotine sometimes differs significantly in physiological activity from S-nicotine (natural) or R-nicotine, such as toxicity, organoleptic properties, etc. The preparation of racemic nicotine is therefore of increasing interest.
At present, racemic nicotine is mainly obtained by artificial synthesis. Starting from different raw materials, the preparation can be synthesized by various routes.
In patent application CN112876454a, 4-methylamino-1- (3-pyridine) butanone hydrochloride is used as a starting material, and racemic nicotine is synthesized by ring closure, dehydration and hydrogenation under the conditions of neutralization and alkalinity.
In Journal of Organic Chemistry,1990, 55 and 1736, pyrrolidine is used as a raw material, and racemic nicotine is synthesized through four steps of reactions of oxidation, coupling, hydrogenation and formylation. The reaction involves harsh experimental conditions such as anhydrous, anaerobic, low temperature, etc.
In Journal of the Chemical Society, perkin Transactions, 2002, 143-154, nicotinic acid is taken as a starting material, is coupled with a bromine-format reagent after condensation reaction, and finally reacts with methylamine hydrochloride to form a ring under the condition of a resin catalyst, and the three steps of reaction are combined. The second reaction step also requires anhydrous and anaerobic operation.
In US patent application US2014031554A1, nicotinic acid is likewise used as starting material and the first two steps are identical, except that the corresponding aldehyde is prepared by reaction with acetone first and finally with methylamine.
In patent applications US2010209006A1, US20160326134, WO2012100722 and CN102617547, methyl nicotinate and N-methylpyrrolidone are taken as raw materials, N-methyl-3-benzoyl-1-pyrrolidone is prepared through condensation reaction under the condition of sodium hydride, and then hydrolysis reaction and reduction reaction under the condition of palladium carbon are carried out to synthesize the racemic nicotine.
It can be seen that the reported method has mainly the following drawbacks: the method has the defects of long route, harsh conditions, low yield, difficult obtainment of initial raw materials and the like, and is difficult to realize industrialized mass production.
Disclosure of Invention
In order to overcome the defects of the prior art, the application provides application of cyclic structure quaternary ammonium base in preparing racemic nicotine, the cyclic structure quaternary ammonium base is brand new, the racemic nicotine can be obtained through one-step synthesis under the catalysis of the cyclic structure quaternary ammonium base, the reaction raw materials are easy to obtain, the reaction steps are few, the reaction byproducts are few, and the method is easy to prepare the racemic nicotine in a large amount.
It is an object of the present application to provide the use of cyclic quaternary ammonium bases for the preparation of racemic nicotine.
It is another object of the present application to provide a quaternary ammonium base of cyclic structure.
It is still another object of the present application to provide a process for the preparation of quaternary ammonium bases of cyclic structure.
It is still another object of the present application to provide a process for preparing racemic nicotine using the cyclic quaternary ammonium base described above.
The aim of the application is realized by adopting the following technical scheme.
In one aspect, the application provides an application of a quaternary ammonium base with a cyclic structure in preparing racemic nicotine.
Preferably, the structure of the cyclic quaternary ammonium base is shown as formula I or formula II:
wherein n is an integer of 1 to 7; t and m are independently integers of 1 to 4.
Preferably, n is an integer from 1 to 4;
preferably, t, m are independently integers from 1 to 2.
Most preferably, the cyclic quaternary ammonium base is selected from:
in another aspect, the present application provides a cyclic quaternary ammonium base having a structure according to formula I or formula II:
wherein n is an integer of 1 to 7; t and m are independently integers of 1 to 4.
Preferably, n is an integer from 1 to 4;
preferably, t, m are independently integers from 1 to 2.
Most preferably, the cyclic quaternary ammonium base is selected from:
the cyclic structure quaternary ammonium base has the characteristics of strong alkalinity, large steric hindrance, strong framework rigidity and the like, and has higher catalytic activity in preparing the racemic nicotine.
In still another aspect, the present application provides a method for preparing the quaternary ammonium base with a cyclic structure, which comprises: takes quaternary ammonium iodized salt as raw material and Ag 2 O undergoes oxidation-reduction reaction to obtainA step to a cyclic quaternary ammonium base; the synthetic route is as follows:
or alternatively
In yet another aspect, the present application provides a method for preparing racemic nicotine using the above cyclic quaternary ammonium base, wherein the cyclic quaternary ammonium base is a catalyst.
Preferably, the method comprises the steps of taking S-nicotine as a raw material, and carrying out one-step reaction under the catalysis of cyclic structure quaternary ammonium base to obtain racemic nicotine, wherein the synthetic route is as follows:
preferably, the method comprises the steps of adding S-nicotine and quaternary ammonium base with a cyclic structure into a solvent-free or organic solvent for reaction by a one-pot method under the protection of inert gas, cooling after the reaction is completed, and purifying to obtain the product.
Preferably, the inert gas is selected from nitrogen, argon or helium.
Preferably, the organic solvent is selected from one or more of toluene, xylene, chlorobenzene, methanol, ethanol, ethyl acetate, chloroform, acetonitrile, ethylene glycol dimethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane and dimethylsulfoxide, preferably selected from one or more of xylene, tetrahydrofuran or dimethylsulfoxide.
Preferably, the temperature of the reaction is 80-200 ℃, preferably 100-150 ℃.
Preferably, the reaction time is 1 to 24 hours, preferably 2 to 10 hours.
Preferably, the molar ratio of the S-nicotine to the cyclic structure quaternary ammonium base is from 100:1 to 100:20.
The method for preparing the racemic nicotine has few reaction steps, easily available raw materials and suitability for large-scale production.
Compared with the prior art, the application provides a brand new quaternary ammonium base with a ring structure, when the quaternary ammonium base with the ring structure is used as a catalyst to prepare the racemic nicotine, the racemic nicotine can be synthesized in one step, and the method adopts S-nicotine as a raw material, and has the advantages of easily available raw materials, fewer reaction steps, fewer reaction byproducts, difficult introduction of other impurities, no introduction of other carbon sources in the preparation, and easy mass preparation.
The cyclic structure quaternary ammonium base has the characteristics of strong alkalinity, large steric hindrance, strong framework rigidity and the like, and has higher catalytic activity in the reaction.
Drawings
FIG. 1 is a liquid chromatogram of racemic nicotine prepared according to the present application (test method reference YC/T561-2018).
Detailed Description
The application will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present application and are not intended to limit the scope of the present application.
Preparation of the catalyst
Example 1: preparation of cat-1
Adding raw material 1 (10 mmol) into a 50mL round bottom flask, adding 25mL water into the flask, stirring the mixture uniformly with a magnet, placing the system into an ice-water bath, and adding Ag into the system in batches 2 O (30 mmol), then the reaction system is slowly restored to room temperature, the reaction is carried out for about 10 hours, and the corresponding cat-1 is obtained after the post-treatment.
The nuclear magnetic data of cat-1 is: 1 H NMR(DMSO-d6,400MHz)；δ:3.68(s,8H)。
example 2: preparation of cat-2
The preparation of cat-2 refers to cat-1.
The nuclear magnetic data of cat-2 is: 1 H NMR(DMSO-d6,400MHz)；δ:2.17(m,4H),3.22(t,8H)。
example 3: preparation of cat-3
The preparation of cat-3 refers to cat-1.
The nuclear magnetic data of cat-3 is: 1 H NMR(DMSO-d6,400MHz)；δ:1.65-1.75(m,8H),3.18-3.35(m,8H)。
example 4: preparation of cat-4
The preparation of cat-4 refers to cat-1.
The nuclear magnetic data of cat-4 is: 1 H NMR(DMSO-d6,400MHz)；δ:1.52-1.83(m,12H),3.16-3.34(m,8H)。
example 5: preparation of cat-5
The preparation of cat-5 refers to cat-1.
The nuclear magnetic data of cat-5 is: 1 H NMR(DMSO-d6,400MHz)；δ:1.42-1.56(m,2H),1.68-1.99(m,3H),2.99-3.28(m,6H),3.30(s,3H)。
example 6: preparation and confirmation of cat-6
The preparation of cat-6 refers to cat-1.
The nuclear magnetic data of cat-6 is: 1 H NMR(DMSO-d6,400MHz)δ:1.22-1.36(m,3H),1.43-1.99(m,4H),3.12-3.38(m,6H),3.31(s,3H)。
example 7: preparation and confirmation of cat-7
The preparation of cat-7 refers to cat-1.
The nuclear magnetic data of cat-7 is: 1 H NMR(DMSO-d6,400MHz)δ:1.42-1.56(m,2H),2.51-2.65(m,1H),2.92-3.43(m,6H),3.35(s,3H)。
preparation of racemic nicotine
The cat-1 to cat-7 used in the following examples were prepared from examples 1 to 7.
Example 8
Under the anaerobic condition, anhydrous toluene, cat-1 (the molar ratio is 1%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, and the reaction is finished after the reactor is heated to 110 ℃ for 1 hour. After completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phase in the system was extracted with toluene, and after the organic phase was combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase is concentrated and distilled under reduced pressure to obtain colorless liquid, and the liquid chromatogram of the prepared racemic nicotine is shown in figure 1, with a yield of 96%.
Example 9
Under the anaerobic condition, anhydrous dimethylbenzene, cat-2 (the molar ratio is 5%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, the mixture is heated to 120 ℃ again, and the reaction is finished after 5 hours. After completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phases in the system were extracted with xylene, and after the organic phases were combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 96% yield.
Example 10
Under the anaerobic condition, absolute ethyl alcohol, cat-3 (the molar ratio is 15%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, and the reaction is finished after the nitrogen balloon is heated to 90 ℃ for 2 hours. After the completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phase in the system was extracted with methylene chloride, and after the organic phase was combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 93% yield.
Example 11
Under the anaerobic condition, cat-4 (molar ratio is 20%), S-nicotine and magneton are added into a reactor, a reflux condenser and a nitrogen balloon are arranged, and the reaction is finished after the reactor is heated to 130 ℃ for 3 hours. After completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phases in the system were extracted with chloroform, and after the organic phases were combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 75% yield.
Example 12
Under the anaerobic condition, anhydrous 1, 4-dioxane, cat-5 (the molar ratio is 2%), S-nicotine and magneton are added into a reactor, a reflux condensing tube and a nitrogen balloon are arranged, the mixture is heated to 120 ℃ again, and the reaction is finished after 10 hours. After the completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phase in the system was extracted with methylene chloride, and after the organic phase was combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 88% yield.
Example 13
Under the anaerobic condition, anhydrous chloroform, cat-6 (the molar ratio is 4%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, and the reaction is finished after the reactor is heated to 100 ℃ for 12 hours. After completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phases in the system were extracted with chloroform, and after the organic phases were combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 87% yield.
Example 14
Under the anaerobic condition, anhydrous methanol, cat-7 (the molar ratio is 6%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, the mixture is heated to 80 ℃ again, and the reaction is finished after 14 hours. After the completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phase in the system was extracted with methylene chloride, and after the organic phase was combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 92% yield.
Example 15
Under the anaerobic condition, cat-5 (mol ratio is 8%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, and the reaction is finished after the mixture is heated to 160 ℃ for 20 hours. After completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phases in the system were extracted with ethyl acetate, and after the organic phases were combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 90% yield.
Example 16
Under the anaerobic condition, anhydrous acetonitrile, cat-3 (the molar ratio is 3%), S-nicotine and magneton are added into a reactor, a reflux condenser tube and a nitrogen balloon are arranged, and the reaction is finished after the mixture is heated to 95 ℃ for 10 hours. After the completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phase in the system was extracted with diethyl ether, and after the organic phase was combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 86% yield.
Example 17
Under the anaerobic condition, adding ethylene glycol dimethyl ether, cat-1 (the molar ratio is 7%), S-nicotine and magneton into a reactor, installing a reflux condenser tube and a nitrogen balloon, heating to 100 ℃ again, and finishing the reaction after 20 hours. After the completion of the reaction, the reaction system was cooled to room temperature, a proper amount of saturated aqueous sodium chloride solution was added to the reaction system, the organic phase in the system was extracted with methylene chloride, and after the organic phase was combined and dried over magnesium sulfate for 30 minutes, celite was filtered. The organic phase was concentrated and distilled under reduced pressure to give a colorless liquid in 90% yield.

Claims (10)

1. Use of cyclic quaternary ammonium base in preparing racemic nicotine.
2. The use according to claim 1, wherein the cyclic quaternary ammonium base has the structure of formula I or formula II:
wherein n is an integer of 1 to 7; t, m are independently integers from 1 to 4;
preferably, n is an integer from 1 to 4;
preferably, t, m are independently integers from 1 to 2;
most preferably, the cyclic quaternary ammonium base is selected from:
3. the quaternary ammonium base with a cyclic structure is shown in a formula I or a formula II:
wherein n is an integer of 1 to 7; t and m are independently integers of 1 to 4.
4. A cyclic quaternary ammonium base according to claim 3 wherein n is an integer from 1 to 4;
preferably, t, m are independently integers from 1 to 2.
5. A cyclic quaternary ammonium base according to claim 3 or 4, wherein the cyclic quaternary ammonium base is selected from:
6. a process for the preparation of the cyclic quaternary ammonium base according to any one of claims 3 to 5, comprising: takes quaternary ammonium iodized salt as raw material and Ag 2 O is subjected to oxidation-reduction reaction to obtain quaternary ammonium hydroxide with a cyclic structure; the synthetic route is as follows:
7. a process for the preparation of racemic nicotine using the cyclic quaternary ammonium base of any one of claims 3 to 5, wherein the cyclic quaternary ammonium base of any one of claims 3 to 5 is a catalyst.
8. The method according to claim 7, wherein the method comprises the steps of taking S-nicotine as a raw material, and carrying out one-step reaction under the catalysis of the cyclic structure quaternary ammonium base to obtain racemic nicotine, wherein the synthetic route is as follows:
9. the method according to claim 7, wherein the method comprises adding S-nicotine and cyclic structure quaternary ammonium base to react in a solvent-free or organic solvent under the protection of inert gas, cooling after the reaction is completed, and purifying to obtain the product;
preferably, the inert gas is selected from nitrogen, argon or helium.
10. The process according to claim 7, wherein the organic solvent is selected from one or more of toluene, xylene, chlorobenzene, methanol, ethanol, ethyl acetate, chloroform, acetonitrile, ethylene glycol dimethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane and dimethylsulfoxide, preferably selected from one or more of xylene, tetrahydrofuran or dimethylsulfoxide;
preferably, the temperature of the reaction is 80-200 ℃, preferably 100-150 ℃;
preferably, the reaction time is 1 to 24 hours, preferably 2 to 10 hours;
preferably, the molar ratio of the S-nicotine to the cyclic quaternary ammonium base is from 100:1 to 100:20, preferably from 100:5 to 100:15.
CN202310977525.XA 2023-08-04 2023-08-04 Application of cyclic quaternary ammonium base in preparation of racemic nicotine Pending CN117000304A (en)

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